Fluoxetine Improve Ability Of Space Learning And Memory Of APP/PS1 Transgenic Mice By Decreased Expression Of AchE And Ruduced Deposition Of Senile Plaques

Objective To discuss whether Fluoxetine improve the ability of learning and space learning memory of APP/PS12×Tg Alzheimer’s Disease Mice. Further to discuss whether the protective effect of Fluoxetine through decreased the expression of AchE and reduced deposition of senile plaques in hippocampus.Methods Experimental animals were divided into two groups:APP/PS1 AD model injection of Fluoxetine (FLU) group (n=6), APP/PS1 AD model saline group (NS) (n=6). After intraperitoneal injection of fluoxetine 10 mg/kg/d for 60 days, Morris water maze test was used to assess the cognitive behavioristics in each group. Nissl staining was applied to quantify neurons in hippocampus. Thioflavin S staining was used to assess senile plagues in hippocampus. Immunohistochemistrical staining was use to analyze the expression of AchE in hippocampus.Results In Morris water maze place navigation trial, the FLU group reduce the time of latency and cumulative distance significantly compared with the NS group (P< 0.05, n=6).There was no significant difference on swimming speed between the two group. In spatial probe trial, the FLU significantly improved the number of crossing the plate. Immunohistochemistry staining of the AchE shows positive intensity in FLU group are less than that of NS group (P< 0.05, n=6). Nissl staining shows that hippocampus neurons in FLU group were significantly more than that of NS group (P< 0.05,n=6); Thioflavin S staining shows that NS group have more senile plaques compared with FLU and NS groups. The number of crossing the plate was negatively related to the IOD of Immunohistochemistry staining of the AchE in area CA1 (r=-791, P= 0.002) and DG (r=-0.839, P= 0.001) of hippocampus.Conclusion Long-term administration of fluoxetine significantly decreased AD model mice AchE expression in hippocampus, reduced senile plaques deposition and improved the ability of learning and memory in APP/PS1 2×Tg Alzheimer’s Disease Mice.